Atypical steroid-like analogue of abiraterone, an inhibitor of androgen biosynthesis, was synthesized and characterized by X-ray diffraction analysis. The in vitro study of the compound by differential spectrophotometric titration revealed its ability to bind to truncated CYP17A1 (D 2-19 variant) in a type II fashion through nitrogen coordination with lower affinity than that of abiraterone, but still in nanomolar concentration range (KD approximate to 187 nM). The significant spectral response (DAmax) value suggests that the new compound effectively targets the conformational ensemble of CYP17A1 accessible for ligand binding.

Novel class of quinoxaline-fused boron subporphyrazines with intense absorption in the range of high transparency of biological tissues (620-650 nm) and stability in common organic solvents comparable with subphthalocyanines were obtained. Two types of macrocycles were presented: quinoxaline fused to subporphyrazine at the 6,7 and 2,3 positions of the quinoxaline ring. During the synthesis of 6,7-quinoxaline-fused subporphyrazines, the formation of chlorinated by-products was observed, and the mono-and dichlorination products were successfully isolated and identified. Conditions for the selective formation of non-chlorinated subporphyrazine were found. The strongest bathochromic shift of the main absorption bands up to 650 nm compared to subphthalocyanines was found for 6,7-quinoxa-line-fused subporphyrazines. Furthermore, 6,7-quinoxaline-fused subporphyrazines demonstrated greater stability in solution compared to their 2,3-quinoxaline-containing analogue. According to this data phenyl-substituted 6,7-quinoxaline-fused subporphyrazine was successfully tested for photodynamic activity against HCT116 cells. Target compound demonstrates high micromolar phototoxicity, accompanied by lipid peroxidation, and low dark cytotoxicity. Thus 6,7-quinoxaline-fused subporphyrazines can be considered as promising competitor to subphthalocyanine photosensitizers for the purposes of photodynamic therapy.

Two series of new diorganotin complexes 1-10, with abiraterone acetate and abiraterone, were synthesized and characterized using 1H, 13C, 119Sn NMR, IR spectroscopy, ESI-MS, and elemental analysis. The anti-inflammatory activity of compounds was evaluated by their inhibition ability toward lipoxygenase. The most active compounds were dibutyltin complexes 4 and 9. Antiproliferative activity in vitro was studied on HCT-116, MCF-7, and PC-3 cancer cell lines, as well as on primary rat skin fibroblasts. Compounds with dibutyltin and diphenyltin moieties (4, 9 and 5, 10, respectively) demonstrated the highest antiproliferative effect, significantly inducing apoptosis in HCT-116 and PC-3 cells and causing the cell cycle arrest at the G2/M phase. These complexes also exhibited significant antibacterial activity comparable to that of ciprofloxacin against the Bacillus subtilis strain. Complex 5 showed antifungal activity against Candida albicans, although it was weaker than metronidazole.

The structures of isoxazole-containing cyclovinylogues of the intracellular fructose transporter protein GLUT5 inhibitor, N-(4-methylsulfonyl-2-nitrophenyl)benzo[d][1,3]dioxol-5- amine (MSNBA) were designed. The target substituted 3,4,5-isoxazoles were synthesized using a method for converting isoxazole-containing enamines to nitriles by their treatment with tert-butyl nitrite in the presence of boron trifluoride etherate. Primary bioassay demonstrated the ability of the target compounds to inhibit the proliferation of chronic myelogenous leukemia cells K562 in medium containing fructose or glucose.

Novel pyrido[1,2-a]benzimidazole-fused tetrapyrrolic photosensitizers with an intense near-infrared absorption (711-747 nm) in the region of high transparency of biological tissues were prepared. Target photosensitizers demonstrated high ΦΔ values (0.49-0.60) resulted from the ability to form triplet states under irradiation. A test with nitroblue tetrazolium showed that in addition to singlet oxygen, they can generate type I reactive oxygen species such as the superoxide anion radical. Water-soluble quaternized forms of target photosensitizers demonstrated low cytotoxicity in the dark and submicromolar phototoxicity against A549, WI38, HCT116, MCF7, A431 and HeLa cell lines. Their phototoxic action is comparable with that of chlorin e6 - a well-known component of the most effective photosensitizers approved for photodynamic therapy, such as Photolon, Photoditazine - but the obtained compounds significantly less cytotoxic in the dark. Using confocal microscopy, it was shown that photosensitizers containing pyrido[1,2-a]benzimidazole cause rapid photoinduced cell necrosis comparable to the necrosis caused by Photolon.

New vitamin E hydrazone analogues bearing (2-hydroxyaryl) methylene moieties were obtained from Trolox hydrazide and the corresponding 2-hydroxyarenecarbaldehydes. The compounds demonstrated effective antioxidant activity and selective action against cancer cells, suggesting their potential as supportive pharmacological agents in oncology.

Platinum(II)-based drugs, such as cisplatin, are commonly used to treat various types of cancer. However, their clinical use is limited due to a number of side effects and the development of resistance. To overcome these limitations, researchers have explored the development of platinum(IV) complexes as potential prodrugs that can be selectively activated under physiological conditions. In this study, we have incorporated synthetic analogs of vitamin E into the structure of platinum(IV) complexes to further improve their safety profile. The antioxidant properties of the compounds were evaluated using DPPH and CUPRAC assays, as well as lipid peroxidation inhibition models, revealing that incorporation of phenolic ligands confers pronounced antioxidant activity. Cytotoxicity was assessed towards cancer cell lines using the MTT assay, where the novel complexes showed significantly increased cytotoxic activity compared to cisplatin, while also demonstrating less toxicity toward normal fibroblast cells under the same in vitro conditions. These results suggest that the conjugation of antioxidant ligands to platinum(IV) scaffolds can modulate both redox processes and the biological activity of the resulting complexes. This proposed design strategy has the potential to create more effective platinum-based cancer treatments with enhanced biological characteristics.

New compounds consisting of 2,6-di-tert-butylphenol and isomeric pyridinecarboxamide moieties as well as their water-soluble hydrochlorides were synthesized. The compounds appeared to be potent antioxidants and radioprotectors, with no significant difference in activity between the pyridine bases and their salts. The cytotoxicity assay showed no significant toxic impact from any of the substances, making them promising candidates for further investigation. Antioxidant and radioprotective moiety Pyridinecarboxylic acid amide fragment

Two series of novel 4-nitro-5-styrylisoxazoles (11 compounds) containing various macrocyclic substituents at positions 3 and 5 of the isoxazole cycle were obtained. Isoxazoles with macrocyclic signal unit in the styryl moiety demonstrated sensor properties in organic solvents to a number of metal cations (Mg(II), Ca(II), Zn(II), La(III), Al(III), Pb(II)). Aggregation-induced emission for the obtained dyes was found in the mixture of DMSO/H2O. In the presence of serum albumin, aggregates of macrocyclic styrylisoxazoles in an aqueous medium dissociated into monomers and formed complex with macromolecule. The compounds demonstrated cytoplasmic distribution in cells in two different forms as aggregates with ‘red’ fluorescence and dyes complexes with cellular proteins with ‘green’ fluorescence, which is promising for studying metabolic processes in the cell.

Novel photosensitizers, isoamyloxy-substituted phthalocyanine complexes containing zinc(II), magnesium(II) and lutetium(III) as central ions, were synthesized by developing a synthetic procedure starting from 4,5-bis(iso-amyloxy)phthalonitrile. Effective approaches were found to obtain 4,5-bis(isoamyloxy)phthalonitrile based on commercially available pyrocatechol. Isoamyloxy-substituted phthalocyanine complexes demonstrated ability to generate reactive oxygen species and fluoresce. To obtain water-soluble forms of phthalocyanines - beta-cyclo-dextrin was used for the delivery of bioactive cargo to the target area. The water-soluble form of the zinc(II) complex exhibited pronounced photodynamic activity in vitro, comparable to chlorin e6.

Novel tripyrrolic photosensitizers covalently linked to drug molecules were obtained by post-macrocyclization functionalization of pyrazine-fused boron subporphyrazines with diclofenac and abiraterone. Improved cyclotrimerization conditions made it possible to obtain the starting boron subporphyrazines with axial chlorine in good yields. The influence of the nature of the axial ligand, as well as peripheral groups, on the photophysical properties of subporphyrazines is shown. The results of flash photolysis showed the formation of triplet states. Compared to diclofenac-substituted compounds, abiraterone-containing photosensitizers exhibited intense fluorescence (Phi(f) similar to 0.2) and high singlet oxygen quantum yields (Phi(Delta) similar to 0.6). In addition to bright fluorescence and efficient singlet oxygen generation, abiraterone-containing subporphyrazines demonstrated micromolar photodynamic activity in vitro and low dark cytotoxicity against a human colon cancer cell line (HCT116). Using thermal lens measurements, a significant increase in the thermal diffusivity of solutions of target subporphyrazines under the influence of laser irradiation was detected.

In this work, stable chemical precursors (3,5-DTBC) and alkylated derivatives were synthesized through strategic modifications guided by the redox and chelation properties of catechol. Leveraging the molecular principle that fusing two bioactive components often yields synergistic effects, catechol — a polyphenol with broad biological activities — was integrated into the nitrogen-containing heterocyclic core structure, imidazolidine-2,4-dione, to design a novel class of hybrid compounds (7a–q) with diverse pharmacological profiles. The primary objective was to explore efficient synthetic routes, characterize structures via physicochemical analyses, and possible evaluate cytotoxicity and AT1-inhibitory activity in vitro.

In this study, we synthesized and characterized new imidazole ligands containing pyridone groups, as well as mononuclear and binuclear ruthenium complexes, which are a new class of water-soluble metallacycles. We studied the antiproliferative activity of these compounds in vitro using the MTT assay on a panel of human cancer cell lines and on primary rat fibroblasts, where we observed a complete absence of cytotoxicity up to a concentration of 1000 µM. For the binuclear metallocycle compounds, we investigated their solubility in water, resistance to hydrolysis, and ability to induce apoptosis in tumor cells.

This review focuses on the main methods for obtaining functionally substituted phthalocyanine complexes, as well as the precursor phthalonitriles containing various hydrophilic and hydrophobic groups. It presents a comparison of the optical and photochemical properties of phthalocyanines, including pathways for generating reactive oxygen species. The potential applications of phthalocyanines are outlined, including photocatalysis, fluorescent diagnostics, and photodynamic therapy for cancer and antibacterial treatments.

A series of organotin carboxylates were synthesized and characterized by NMR (H-1, C-13, Sn-119) and IR spectroscopy, ESI mass-spectrometry and elemental analysis. The structure of two compounds was resolved directly using X-ray diffraction analysis and unusual heptacoordinated Sn coordination polyhedron was discovered for them. Antioxidant activity of the synthesized compounds was estimated using DPPH, NBT and CUPRAC-tests, lipid peroxidation and lipoxygenase inhibition capacity as well. It was shown that the presence of the hydroxyl group in the aromatic ring of the ligand drastically increases antioxidant potency of the complexes, while not noticeably affecting the antiproliferative properties, which were measured with the standard MTT-test. Moreover, it was shown that derivatives of dibutyl- and di-tert-butyltin exhibit the highest cytotoxicity. Three complexes were put forward as lead compounds and additional apoptosis induction studies were carried out. Noticeable caspase activation was shown for the complexes 4 and 7 thus marking their mode of action. The results obtained show that the complexes herein described are promising antiproliferative agents.

Aim. To identify the most suitable pathogenetic mechanisms for in-depth study of the antitumor and antimetastatic effects of tested hybrid organotin compounds using the immunohistochemical approach.Materials and Methods. Here, we tested bis(3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethyltin (laboratory code Me-3), belonging to the class of hybrid organotin compounds, on 30 female C57Bl/6 mice using a universal model of transplantable tumors with spontaneous metastasis (B16 melanoma). 48 hours after tumor cell transplantation, we intraperitoneally administered Me-3 once daily to female C57Bl/6 mice for 10 days at a total dose (TD) of 375 mg/kg. For histological analysis, we used the primary tumor node of B16 melanoma. Immunophenotyping of B16 melanoma tissue samples was carried out using the polyclonal antibodies to transforming growth factor beta 1 (TGFβ-1), vascular endothelial growth factor A (VEGFA), Bcl2-associated X Protein (Bcl-2), cluster of differentiation 34 (CD34).Results. After the exposure to Me-3, we found a reduced immunohistochemical signal to TGF-β1 and Bcl-2 3 in the tumor tissue. Low doses of Me-3 have also impacted angiogenesis.Conclusion. Me-3 has a pro-apoptotic and anti-angiogenetic effects on B16 melanoma cells in C57Bl/6 mice.

Complexes of various metals have a broad scope of applicability as luminescent materials. These compounds are used both as components of displays, batteries, and semiconductors and in the fields of biology and medicine. This review describes complexes containing group 13, 14, and 15 elements in the molecules, which can be considered as promising luminophores. Their photophysical properties and some aspects of physiological activity are presented.

New ruthenium(ii) and ruthenium(iii) complexes with 2,6-di-tert-butylphenol as the antioxidant moiety were synthesized, and their antioxidant and antiproliferative activities were evaluated. Electrochemical behaviour and the potential of these compounds to act as inhibitors of lipid peroxidation in biological systems were explored.

Steroid dimers of natural and synthetic origin possess an unusual and complex molecular architecture that may lead to the realization of peculiar effects in biological systems, in particular in different cancer cell lines. In the present work, diastereoselective ring-opening of mono- and polyoxiranes, containing a cyclooctane core, by azide-anion was performed to yield a series of azidoalcohols with different types of symmetry. The products were involved in copper-catalyzed azyde-alkyne cycloaddition (CuAAC) reaction with ethinylestradiol and ethinyltestosterone, and the resulting steroids and steroid dimers with triazole linkers were screened for their antiproliferative activity via (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) assay. All the compounds revealed cytotoxicity toward several cancer cell lines. The effect of the most potent compound, containing two estradiol moieties, on the microtubules (MT) dynamics was investigated by immunofluorescent microscopy. The disruption of the majority of interphase cell cytoplasmic MT and mitotic event disturbances in the presence of the studied compound were observed. The latter effect caused the appearance of numerous multinucleated cells.

ABSTRACT A large series of previously unknown isoxazole containing difluoroboron β‐diketonate has been designed and synthesized from the available starting compounds. The photophysical properties of obtained compounds were studied, and the effects of the substituents in aromatic and isoxazole cycles of the BF 2 complexes on the fluorescence were investigated. The effect of solvatochromism were demonstrated. Cytotoxic activity against MCF‐7 (breast carcinoma), HCT‐116 (colon carcinoma), A549 (pulmonary carcinoma) and WI38 (fibroblasts from lung tissue) cell lines was tested and moderate toxicity in the concentration range of 10–100 μM was found for several compounds.